A Photocontrolled Molecular Switch Regulates Paralysis in a Living Organism
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Using light to modulate biochemical agents in living organisms has a significant impact on photodynamic therapy and drug release. We demonstrate that a photoresponsive system can reversibly induce paralysis in nematodes as a model for living organisms when two different wavelengths of light are used to toggle the molecular switch between its two structural forms. This example illustrates how photoswitches offer great potential for advancing biomedical technologies.The study of the single neuron response to photodynamic effect provides information on the dynamics of cytotoxic events leading to cell death and allows comparison of the phototoxicity of different photosensitizers. Isolated crayfish stretch receptor neurons were incubated 30 min with different concentrations of various photosensitizers and then irradiated with a He-Ne laser (632.8 nm; 0.3 W/cm/sup 2/) until irreversible firing abolition. The dynamics of neuron impulse response was continuously recorded throughout the experiment. The following photosensitizers were studied: hematoporphyrin derivatives Photoheme and Photofrin II, 6 deuteroporphyrin IX derivatives and sulphonated aluminum and zinc phthalocyanines. Nerve cells were found to be insensitive to either He-Ne laser irradiation or photosensitization alone, but very vulnerable to photodynamic effect: neurons changed their firing rate and irreversibly ceased their impulse activity at nanomolar (phthalocyanines and hematoporphyrin derivatives) and even pikomolar (deuteroporphyrin derivatives) concentrations of photosensitizers. The dynamics of the neuron responses to photodynamic effects included stages of firing activation and/or inhibition followed by irreversible firing abolition. It depended on the photosensitizer type and concentration. Decrease of extracellular pH or action of pharmacological agents increasing intracellular Ca/sup 2+/ concentration or inhibiting ATP synthesis exacerbated photodynamic neuron injury. In contrast, agents decreasing intracellular calcium concentration or bioenergetic substrates protected the neuron against photodynamic injury. The dependencies of neuron lifetimes on the photosensitizer concentration provide comparison of photodynamic efficiencies of different photosensitizers.
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According to recent advances in nanotechnology, various nano-sized formulations have been designed for the application in biomedical fields, including diagnosis, drug delivery, and therapeutics. The nanotechnology-based formulations have a great merit in the design of multifunctional platform for the biomedical applications. Therefore, recent trends in nanotechnology are moving onto the combination of nanotechnology and conventional therapeutic. Typically, photodynamic therapy (PDT) is one of promising techniques for the combination with nanotechnology owing to its less invasiveness. In this paper, we are going to briefly review recent advances in nanotechnology-based PDT, including selective delivery and excitation of photosensitizers, combination therapy, and multifunctional PDT.
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The Rockefeller Institute for Medical Research has been appealed to by so many physicians and laymen for information and advice on the subject of infantile paralysis that it has seemed desirable to relate the facts of present knowledge concerning certain highly pertinent aspects of the disease, together with deductions of practical importance derived from them.
Nature.
—Infantile paralysis is an infectious and communicable disease which is caused by the invasion of the central nervous organs—the spinal cord and brain—of a minute, filterable micro-organism which has now been secured in artificial culture and as such is distinctly visible under the higher powers of the microscope.Location of the Micro-Organism or Virus in the Sick.
—The virus of infantile paralysis, as the micro-organism causing it is termed, exists constantly in the central nervous organs and on the mucous membrane of the nose and throat and of the intestines in persons suffering fromThroat
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Photodynamic therapy (PDT) is a highly effective, noninvasive, highly selective method for cancer treatment. Nanoscale metal-organic frameworks (NMOFs) are a type of crystalline hybrid material composed of metal centers and organic linkers. Owing to their adjustable structure, easy modification, permanent pores, and good biocompatibility, NMOFs, as either nanophotosensitizers or photosensitizer nanocarriers, have been used in PDT. In this article, we summarize the recent progress in MOF-based nanomaterials for tumor PDT. The MOF-based nanomaterials might open up new avenues for the fabrication of new types of photosensitizers for PDT.
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1. The attempt to infect young rabbits and guinea pigs with material containing in all probability the virus of human infantile paralysis failed. 2. Failure to infect the primary animals almost of necessity brought failure with the secondary flea-bitten animals. It is, however barely conceivable that a non-infectious form of an organism might circulate in the blood of the primary animal and that this form, through development in an intermediate host, the flea, might become virulent for the secondary flea-bitten animal. 3. Incidentally, and presumably accidentally, a paralytic disease was observed in young rabbits associated with the presence of an organism showing certain definite characters. So far as we know this paralysis and the associated organism have not been previously described. 4. This organism is found widely distributed in the organs of the affected animals and can be demonstrated in the urine. The active destruction by the organism of the nerve cells of the spinal cord is particularly striking, and gives complete explanation for the paralysis observed clinically. 5. With the organism present in the urine the spread of the disease by contact can be easily understood. 6. The transfer of the infection from animal to animal by fleabites is possible but not probable. 7. The nature of the observed organisms is in doubt. They represent probably an intermediate stage in the life history of some protozoan parasite.
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Photodynamic therapy (PDT) provides an effective option for treatment of tumors and other diseases in superficial tissues and attracts attention for in vitro study with cells. In this study, we present a significantly improved model of in vitro cell killing through Type-II PDT for simulation of the molecular interactions and cell killing in time domain in the presence of oxygen transport within a spherical cell. The self-consistency of the approach is examined by determination of conditions for obtaining positive definitive solutions of molecular concentrations. Decay constants of photosensitizers and unoxidized receptors are extracted as the key indices of molecular kinetics with different oxygen diffusion constants and permeability at the cell membrane. By coupling the molecular kinetics to cell killing, we develop a modeling method of PDT cytotoxicity caused by singlet oxygen and obtain the cell survival ratio as a function of light fluence or initial photosensitizer concentration with different photon density or irradiance of incident light and other parameters of oxygen transport. The results show that the present model of Type-II PDT yields a powerful tool to quantitate various events underlying PDT at the molecular and cellular levels and to interpret experimental results of in vitro cell studies.
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